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Polyglutamine diminishes VEGF; passage to motor neuron death?
1Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
Abstract:
Altered gene transcription has been implicated in the pathogenesis of polyglutamine-dependent neurodegeneration. In this issue of Neuron, Sopher et al. demonstrate that androgen receptors containing expanded polyglutamine cause decreased expression of vascular endothelial growth factor (VEGF) by interfering with cAMP response element binding protein binding protein (CBP), thereby contributing to the motor neuron degeneration in spinal and bulbar muscular atrophy.
Insights
Expanded polyglutamine in androgen receptors disrupts vascular endothelial growth factor (VEGF) expression by interfering with cAMP response element binding protein binding protein (CBP). This mechanism contributes to motor neuron degeneration in spinal and bulbar muscular atrophy.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Polyglutamine-dependent neurodegenerative diseases are linked to altered gene transcription.
- Spinal and bulbar muscular atrophy (SBMA) is a polyglutamine disease affecting motor neurons.
Discussion:
- Expanded polyglutamine in androgen receptors impairs vascular endothelial growth factor (VEGF) expression.
- This impairment involves interference with the cAMP response element binding protein binding protein (CBP) coactivator.
- The reduced VEGF levels contribute to motor neuron degeneration in SBMA.
Key Insights:
- Androgen receptor polyglutamine expansion directly impacts gene expression crucial for neuronal survival.
- CBP's role as a mediator in polyglutamine-induced transcriptional dysregulation is highlighted.
- A specific molecular mechanism linking androgen receptor dysfunction to VEGF deficiency in SBMA is elucidated.
Outlook:
- Targeting the interaction between androgen receptors and CBP may offer therapeutic strategies for SBMA.
- Further research into VEGF signaling pathways in neurodegeneration could reveal new treatment avenues.
- Understanding polyglutamine-mediated transcriptional changes is vital for developing treatments for related neurodegenerative disorders.
